Recent neuroimaging studies indicated that structural abnormalities may occur in late life depression, but the extent of these changes and their relationship to clinical and behavioral measures, especially inpatients presenting at primary care settings, remains unknown. The primary objective of this proposal is to examine the neuroanatomical and cerebrovascular basis of late life major depression in subjects presenting at geriatric primary care sites. We hypothesize that gray and white matter atrophy underlie late life major depression and structural changes in the white matter will correlate with cerebrovascular risk factors. While neuroanatomic studies provide us with a better understanding of normal and abnormal brain function, the integration of neuroanatomic data with clinical and behavioral measures is critical for a broader and more complete understanding of the pathogenesis of late life depression. This proposal will examine the relationship between global and focal structural changes and important variables such as cerebrovascular risk factors, age of onset of illness and sex differences in neuroanatomy. Neuroanatomic abnormalities alone are unlikely to be the sole cause of depression in late life and this study will help us examine the relative roles of anatomical changes, cerebrovascular risk factors and medical illness in the pathogenesis of late life major depression.